Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma

Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread.     

Data Mining and the Implementation of a Prospective Payment System for Inpatient Rehabilitation

This paper describes the development of a new Medicare Prospective Payment System (PPS) for inpatient rehabilitation care. Congress mandated such a system in the Balanced Budget Act of 1997. To help implement this system, we assembled four years of Medicare hospitalization data, linked it to rehabilitation hospitals' information about impairment and the functional status of patients, and developed case mix groups using the CART algorithm, a common method for determining groups in health services.While CART readily produces simple and effective rules for prediction, it adheres to a restrictive functional form and its fitting algorithm does not necessarily produce a global optimum. We wanted to know how these limitations affect our results. So, we compared CART's performance with methods receiving attention in the data mining community and in the statistics literature. We estimated that the CART models explained about 90 percent of the potentially explainable variance in individual cost and they predicted annual hospital costs that were essentially identical to other methods' predictions.     

Disease tropism of c-erbB: effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation.

Avian leukosis virus induces erythroleukemia in chickens by proviral insertional mutation of the protooncogene c-erbB. The product of the insertionally activated c-erbB locus lacks the extracellular ligand-binding domain and is strictly leukemogenic. It has previously been demonstrated that the disease spectrum associated with aberrant c-erbB expression can be expanded by structural perturbation of the cytoplasmic domain of this protein. In this report, we use mutagenesis and retroviral vectors to identify specific mutations in the carboxyl-terminal domain of the insertionally activated c-erbB product that are sufficient to activate the sarcomagenic potential of this protein. Interestingly, a point mutation in the kinase domain appears to be sufficient for sarcomagenic activation. However, removal of the terminal tyrosine residue of the c-erbB product, implicated in modulating kinase activity, does not lead to a fully transforming phenotype. These studies suggest that there are multiple ways to activate the fibroblast-transforming potential of the insertionally activated c-erbB product. The conformation of this protein may play a more significant role in oncogenic activation than the phosphorylation status of the putative carboxyl-terminal autophosphorylation site.     

The AT2 angiotensin receptor subtype predominates in the 18 day gestation fetal rat brain

The angiotensin II receptor subtype-specific antagonists Dup 753 (AT₁) and PD 123177 (AT₂) were used to characterize the angiotensin II receptor subtypes present in 18 day gestation fetal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rat brain using in vitro receptor autoradiography. The AT₂ subtype was predominant in the brain of both rat strains, even in areas that display predominantly the AT₁ subtype in the adult rat brain.